A number of test systems has been developed in our laboratory for evaluating drugs potentially useful in human cancer of the prostate. The systems have relied on unique features of the prostate and include the following: 1) the effects on 5 alpha-reductase and arginase activity in the rat prostate; 2) the effects on the deposition of labeled androgens and estrogens in the dog and baboon prostates; 3) the incorporation and distribution of labeled zinc in the rat and baboon prostates; 4) the development of an organ culture system utilizing animal and human prostate explants and the effects of various chemotherapeutic drugs on the parameters listed above in such explants of the prostatic tissue in organ culture; and 5) the effects of various drugs (singly or in combination) on rat prostatic cancers. Newer approaches will involve 6) the determination of the chromosomal changes in human and animal prostatic tumors and correlation with therapeutic and other parameters; and 7) the use of sister chromatid exchange (SCE) as a means of detecting drugs possibly effective in cancer of the prostate. SCE will be determined in either normal and/or cancerous human prostatic cells in culture. Our ultimate aim is to expand the testing of the effects to a large group of new and "old" anti-cancer agents, utilizing approaches which afford a direct evaluation of the effects of drugs on human cancers of varying histology and drug sensitivity.